Management of Patients with Acute Methotrexate Nephrotoxicity with High‐Dose Leucovorin

Flombaum, Carlos D.; Liu, Dazhi; Yan, Shirley Qiong; Chan, Amelia; Mathew, Sherry; Meyers, Paul A.; Glezerman, Ilya G.; Muthukumar, Thangamani

doi:10.1002/phar.2145

Cited by 24 publications

(26 citation statements)

References 15 publications

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“…Osteosarcoma is defined as a malignant spindle cell tumor which produces osteoid (Fletcher et al 2013). Despite being a genetically complex tumor, its diagnosis is not based on any molecular testing at present (Gorlick 2009), but on routine hematoxylin and eosin staining and conventional light microscopy.…”

Section: 6mentioning

confidence: 99%

“…Osteosarcoma demonstrates that treatment success will only be achieved through close interdisciplinary collaboration. The most common subtype, high-grade central osteosarcoma, carries a very high risk of systemic dissemination, so that surgery alone will rarely lead to cure (Casali et al 2018;Fletcher et al 2013;Jaffe 1972;Link et al 1986;Marcove et al 1970). Chemotherapy without sufficient local therapy will also result in failure (Bielack et al 2002;Jaffe et al 2002).…”

Section: Introductionmentioning

confidence: 99%

“…Rare low-grade central, parosteal, and periosteal osteosarcoma variants are of lower malignant potential and treated by surgery alone (Casali et al 2018;Cesari et al 2011;Fletcher et al 2013;Grimer et al 2005;Laitinen et al 2015). Craniofacial osteosarcomas also carry a lower risk of metastatic spread, but a high risk of local failure, and recent guidelines favor a multidisciplinary approach (Casali et al 2018).…”

Section: Introductionmentioning

confidence: 99%

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Osteosarcoma-Approach to Therapy

Bielack

Cable

Görlick

et al. 2020

Sarcomas of Bone and Soft Tissues in Children and Adolescents

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Section: 6mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Osteosarcoma-Approach to Therapy

Bielack

Cable

Görlick

et al. 2020

Sarcomas of Bone and Soft Tissues in Children and Adolescents

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“…Two recent studies have brought into question the benefits of glucarpidase over high-dose leucovorin and supportive care. Flombaum et al 44 examined 88 patients, who received 100 courses of HDMTX and had MTX levels 10-fold or more than the threshold for toxicity at 48-72 h post-administration. Of these, 81% received high-dose leucovorin per institutional protocol.…”

Section: Glucarpidase Versus High-flux Hdmentioning

confidence: 99%

High-flux hemodialysis versus glucarpidase for methotrexate-associated acute kidney injury: What’s best?

Kitchlu

Shirali

2019

Journal of Onco-Nephrology

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Kidney-related adverse drug effects from chemotherapeutic agents can cause acute kidney injury that may influence cancer treatment and patient outcomes. Many current chemotherapy drugs are associated with acute kidney injury, including methotrexate which causes dose-dependent tubular injury. In this review, we will focus on the manifestations of kidney disease secondary to methotrexate and discuss management strategies. In particular, we will review the use of high-flux hemodialysis versus glucarpidase for reducing toxic serum levels of methotrexate.

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“…However, all deaths were ruled unrelated to glucarpidase by the patient’s treating physician. In Flombaum et al’s2 observational study on seven cancer patients treated with glucarpidase, one patient expired due to complications related to sepsis. Additional research on the impact of the time of glucarpidase administration was conducted by Ward et al,1 who concluded that increased patient mortality was associated with delayed administration.…”

Section: Introductionmentioning

confidence: 99%

<p>Length of stay, mortality, and readmissions among Medicare cancer patients treated with glucarpidase and conventional care: a retrospective study</p>

Demiralp¹,

Koenig²,

Kala³

et al. 2019

CEOR

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PurposeGlucarpidase (Voraxaze) is used to treat methotrexate (Mtx) toxicity in patients with delayed Mtx clearance due to impaired renal function. We examine hospital length of stay (LOS), mortality, and readmission rates for Medicare cancer patients with delayed clearance of Mtx treated with glucarpidase.MethodsUsing 2010–2017 Medicare claims data, we identified glucarpidase patients as those hospitalized with indications of select lymphomas or leukemia, inpatient chemotherapy, and glucarpidase treatment. We assessed outcomes of glucarpidase patients relative to those experienced by patients treated for presumed Mtx toxicity using other therapies. These nonglucarpidase patients were identified with a diagnosis of primary central nervous system lymphoma, indications of cancer-chemotherapy toxicity, and acute kidney injury during hospitalization (not present on admission), and were divided into two groups: treated with dialysis (dialysis+) and treated with or without dialysis (dialysis+/−). Inverse-probability treatment weighting using propensity scores was used to adjust for differences between groups.ResultsPatients treated with glucarpidase (n=30) had an average LOS of 14.7 days. They had inpatient, 30-day, and 90-day mortality rates of 3.3%, 13.3%, and 16.7%, respectively, and a 90-day all-cause unplanned readmission rate of 24.1%. The dialysis+ and dialysis+/− groups, respectively, had higher average LOS (40.2, 21.9), higher inpatient mortality (50.6%, 20.8%), and higher 90-day mortality (58.6%, 37.6%). No statistically significant differences in 30-day mortality or 90-day readmission rates were detected between the glucarpidase group and either of the nonglucarpidase groups. Unobservable differences in patient severity may impact the interpretation of our findings.ConclusionMedicare cancer patients with presumed Mtx toxicity receiving conventional treatment experience long hospitalizations, high intensive-care unit use and high mortality. Glucarpidase patients had lower LOS, inpatient mortality, and 90-day mortality than the non-glucarpidase patients.

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Management of Patients with Acute Methotrexate Nephrotoxicity with High‐Dose Leucovorin

Cited by 24 publications

References 15 publications

Osteosarcoma-Approach to Therapy

Osteosarcoma-Approach to Therapy

High-flux hemodialysis versus glucarpidase for methotrexate-associated acute kidney injury: What’s best?

<p>Length of stay, mortality, and readmissions among Medicare cancer patients treated with glucarpidase and conventional care: a retrospective study</p>

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